The SARS-CoV-2 responsible for the Coronavirus disease 2019 (COVID-2019) outbreak represents a major public health threat that urgently requires development of a small animal model that can be used to test medical countermeasures. This supplement proposal is a logical extension of our parent grant, Development a VLP Vaccine for RSV (PO: Sonnie Kim, R44 AI109926). The laboratory of the PI and his collaborators specialize in both, developing new vaccines, vaccination strategies, and therapies to overcome viral infection and viral-induce Acute Respiratory Distress Syndrome (ARDS), and into the development new model of human respiratory viral infectious diseases. The cotton rats is known for their outstanding translational value for human health and, in contrast to mice, are highly susceptible to infection with non-adapted human viruses, including those that specifically target the respiratory tract. Cotton rats are also notoriously difficult to work with, and SBI has the utmost experience and capabilities required to work with these animals. We are in a position to offer our decades-long expertise in the cotton rat model to develop fully a SARS-CoV-2 model of infection that can recapitulate Acute Respiratory Distress Syndrome (ARDS) induced by SARS-CoV-2 and be used for an expedient and reliable testing of experimental therapeutic and vaccine candidates. All resources are in place for the rapid start of work, including our in- house colonies of two different species of inbred cotton rats (Sigmodon hispidus and Sigmodon fulviventer), We have established very strong collaboration with Bioqual Inc., a close by company with which we have collaborated in the past for many projects, including a SBIR phase II. They will provide both, ABSL3 and BSL3 facilities, as well as experienced personnel, and the newly isolated SARS-CoV-2 virus. With this highly-regarded team of senior scientists recognized for the expertise in developing novel cotton rat models and for their expertise in targeting innate immune pathways, we hypothesize that cotton rats will recapitulate ARDS observed in recent human cases of SARS-CoV-2 infection and become a reliable small animal model for screening newly developed vaccines and therapeutics, such as TLR4 antagonists, that will result in a more rapid medical countermeasure.